Debra Wood, RN

Heart-lung complications are more likely in survivors of these cancers:

The treatments listed below have been found to sometimes be associated with the listed conditions (in many instances, these side effects are rare):

> Anthracyclines (Adriamycin/doxorubicin and Ellence/epirubicin): inflammation of heart, cardiomyopathy, heart failure

> Cytoxan (cyclophosphamide): inflammation of heart, cardiomyopathy, heart failure 

> Cisplatin: inflammation of heart, cardiomyopathy, heart failure 

> Taxanes (Taxol/paclitaxel and Taxotere/docetaxel): inflammation of heart, cardiomyopathy, heart failure

> Herceptin (trastuzumab): lung inflammation, heart failure 

> Blenoxane (bleomycin): lung scarring, inflammation, pneumonia

> Carmustine: lung scarring, inflammation, pneumonia

> Methotrexate: lung scarring, inflammation

> inflammation of the sac surrounding the heart, scarring or inflammation, valve damage, irregular heart rate, coronary artery disease

> lung scarring, pneumonitis, possibly progressive pulmonary fibrosis; late complications include right-side heart failure and respiratory failure 

Bone marrow or stem-cell transplantation:

> interstitial pneumonitis: a group of disorders related to the sacs in the lungs where air exchange takes place; late complications include idiopathic pneumonia syndrome, injury to the sacs where air exchange takes place in the lungs; and bronchiolitis obliterans, inflammation of the bronchioles, small airways in the lung

Experts do not recommend routine screening tests, beyond an annual physical exam with a blood pressure check and blood work to check cholesterol levels. 

SOURCES: American Society of Clinical Oncology “Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects”; Institute of Medicine, “From Cancer Patient to Cancer Survivor: Lost in Transition”

Articles

Heart-lung complications are more likely in survivors of certain cancers&mdash;breast, lymphoma, testicular, lung&mdash;and who received certain treatments

What to Watch For

Although common and of concern to patients, nausea and vomiting need not result from treatment. The American Cancer Society reports as many as 80 percent of patients experience nausea and vomiting during chemotherapy, but medication and other management options offer patients a break. While not all nausea can be prevented or treated, much progress has been made in calming a queasy stomach. 

 Chemotherapy agents stimulate certain parts of the digestive tract, as well as a specific area of the brain that controls vomiting. The risk of developing nausea and vomiting during chemotherapy depends on the agent, the dose, frequency given, route of administration, and patient factors such as age. Certain drugs, such as cisplatin and Adriamycin (doxorubicin), are more closely associated with this side effect. High doses of intravenous chemotherapy given frequently also increase the chance of gastrointestinal distress. Brain metastasis or tumors that obstruct the bowel can also cause such symptoms.

Nausea and vomiting more often occur with total body irradiation or radiation focused close to the abdomen or small bowel than with radiation to the arm, leg, head and neck, or breast.

The onset of nausea and vomiting can vary, with acute nausea and vomiting happening within minutes or several hours after treatment, and delayed nausea developing more than 24 hours after chemotherapy. Anticipatory nausea and vomiting occurs when a prior bad experience with treatment is triggered by certain aspects of the clinic visit and treatment.

Severity of nausea and vomiting is graded from one to five, with one being mild and five being death from complications such as dehydration. Nausea and vomiting can produce other serious consequences, including esophageal tears, aspiration of food into the lungs, wounds not healing, stopping treatment, and loss of functional ability.

The best defense against nausea and vomiting is to stop it from happening in the first place by using antiemetic drugs. With chemotherapy agents likely to cause acute nausea and vomiting, the American Society of Clinical Oncology recommends a three-drug combination. The regimen includes a 5-HT3 antagonist—Anzemet (dolasetron), Kytril/Sancuso (granisetron), Zofran (ondansetron), or Aloxi (palonosetron)&mdash;given before chemotherapy, plus the steroid dexamethasone for one to three days, and the NK-1 receptor antagonist Emend (aprepitant) for three days. These medications work differently and have differing methods of delivery (oral, I.V., or skin patch).

With agents that have a moderate risk of causing nausea and vomiting, evidence suggests the drug combination without Emend is effective; with low-risk agents, only dexamethasone; and for minimal risk, no treatment unless the patient has experienced prior vomiting with therapy.

ASCO recommends patients undergoing total body irradiation receive a 5-HT3 antagonist before treatment, with or without dexamethasone. With radiation to the abdomen, chest, brain, or back, the organization suggests a similar plan without the steroid.

If the patient cannot tolerate or doesn’t respond to the first-choice drugs, the physician may order a different antinausea medication, a synthetic cannabinoid such as Marinol (dronabinol) or Cesamet (nabilone), and/or a dopamine receptor antagonist.

For anticipatory nausea and vomiting, the doctor may suggest anti-anxiety medications or nondrug interventions, such as relaxation and distraction, to decrease anxiety. Acupressure, acupuncture, and guided imagery may be used in conjunction with medication. Trials researching the use of herbs, such as ginger, and other natural supplements are under way, but the effectiveness of these products is not established.

 Patients can take nonmedical steps to stave off nausea. Self-care techniques include eating a snack prior to chemotherapy or an hour before radiation and bringing food if the treatment will last a long time. Patients may better tolerate small, frequent meals served at room temperature and easy-to-digest items, such as crackers, toast, or flat ginger ale. Patients should wear loose-fitting clothes, and limit exposure to sounds, sights, and smells that trigger nausea.  

How to avoid nausea and vomiting during treatment. 

Squashing a Queasy Stomach

An opportunity to obtain whiter teeth at less cost saved Dave Edler much more than money. His new dentist took one look at his mouth and recognized a sore as a potential cancer. “If not for her, I’d have let it go, and it would have gotten out of hand,” says Edler, of Alton, Ill. “She was on it.” 

Edler thought his dry, cracked lip resulted from motorcycle riding. His previous dentist had never said anything. But Danielle Csaszar, DMD, formerly at College Avenue Family Dentistry in Alton, recognized the need for further evaluation and treatment. A biopsy revealed oral cancer, and a plastic surgeon was able to remove the entire lesion without long-term disfigurement.

“If not for the dentist looking at it, it could have been ugly,” Edler says. “It didn’t dawn on me that this could happen.”

Similarly, Thomas Camacho Jr. of Gainesville, Fla., is grateful that William Harriett, DMD, at University Family Dentistry in Gainesville, found a suspicious sore in his mouth, allowing him to receive early treatment with radiation. 

“I’m elated he found it,” says Camacho, who has been in remission for nine years. “If it hadn’t been for him, I wouldn’t have gotten it treated.”

Some 34,000 people learned they had cancer of the oral cavity or pharynx (the upper portion of the throat) last year, according to estimates by the American Cancer Society. More than 7,500 people with this type of cancer die annually, and only about 60 percent live five years or longer, the ACS reports.

“The five-year survival rate hasn’t changed in 50 years,” says Arlen D. Meyers, MD, MBA, professor of otolaryngology at the University of Colorado Denver School of Medicine. “The five-year survival has not changed because most people present with relatively advanced disease.”

The cancer may occur on the lips, tongue, gums, cheek lining, mouth or throat. But because the sore or tumor may cause no pain, the patient often remains unaware of the problem. Doctors often find oral/pharyngeal cancer after it has spread to the lymph nodes or beyond.

Men are more likely to develop oral/pharyngeal cancer than women. Traditionally, most oral cancer has occurred in people age 40 or older. But recent trends show an increase of cases in younger people.

Edler and Camacho learned about their cancers at an early stage thanks to dentists assessing for problems in the mouth, beyond just the teeth. 

“Dental screening for oral cancer is critical,” says A. Ross Kerr, DDS, MSD, clinical associate professor in the department of oral and maxillofacial pathology, radiology and medicine at New York University. “The earlier you catch it, the better off you are.”

A dentist completing a screening will ask about the patient’s health history and habits such as smoking and alcohol use that could increase risk. During the physical exam, he or she will feel the neck and check for sores on the lips or skin. Then the dentist will look inside the mouth, using a regular dental light, and will check for sores and feel for bumps. The dentist should move the tongue from side to side.

“It takes less than 90 seconds to look everywhere very well,” says Gustavo D. Cruz, DMD, MPH, associate professor of epidemiology and health promotion at the New York University College of Dentistry. “It should be part of the regular examination. It’s noninvasive.”

A suspicious spot might prompt the dentist to employ additional tools, such as applying dyes and stains, collecting cells or using a special light (see sidebar, next page). For example, the dye toluidine blue might help the dentist find the best place to obtain a biopsy, Kerr explains. 

Even if a supplemental tool is used, a biopsy must confirm the diagnosis, Cruz says.

Doctors often will surgically remove the tumor. They also might treat it with radiation and, for advanced cancers, chemotherapy might be added. Treatment, however, often leads to disfigurement or difficulty eating and drinking. While the use of chemotherapy and radiation may allow for less extensive surgery, long-term side effects of therapy, such as dry mouth and ongoing dental problems, can ensue.

Second primary tumors will develop in 10 percent to 40 percent of patients, according to the cancer society.

American Dental Association spokesman Sol Silverman Jr., DDS, professor of oral medicine at the University of California, San Francisco School of Dentistry, recommends that survivors of oral/pharyngeal cancer obtain close follow-up care and limit exposure to risk factors. Treatment becomes more complex for a second tumor, but is possible.

Silverman considers it essential that dentists educate patients about lowering their risks. 

“Dentists and dental hygienists are part of the health team. And they have to take these things into consideration with the examination and advising [patients] about what to do and not to do,” Silverman says.

Risk factors include use of tobacco and excessive alcohol intake. Human papillomaviruses may be a factor in 20 percent to 30 percent of cases. Other factors including sun exposure, poor nutrition and a suppressed immune system also may play a role.

Unfortunately, not everyone sees a dentist regularly. And many people are not able to afford dental care.

Many patients at risk for advanced oral cancer and late diagnosis are those with low socioeconomic status. “Those are usually the people with poor access to dental care,” Cruz says.

Another challenge stems from dentists’ knowledge of and comfort levels with screening. 

“Most general dentists are not adequately trained to screen, or feel uncomfortable doing it,” Meyers adds.

Newer dentists learn about the screening in school. But those practicing for more than 10 years may not be as familiar with the techniques. To address such concerns, the state of New York mandates that dentists complete a two-hour continuing education course covering oral cancer, early detection and tobacco cessation.

And while screening to find cancers early seems like a good idea, little evidence exists that it leads to improved health outcomes, according to the U.S. Preventive Services Task Force and the National Cancer Institute. The task force does not recommend for or against screening. 

The American Dental Association, however, encourages dentists to perform a screening. If a dentist does not do such an exam, Silverman suggests patients inquire about it. 

“Ask the dental hygienist or dentist at the next checkup to please check for oral cancer. It doesn’t cost anything,” Cruz adds. “It takes so little time, doesn’t do any harm, and it could be a perfect teaching moment for patients at risk.”

Many professionals agree that noninvasive oral screenings by dentists are a good idea. Silverman says he has no doubt about the benefit.

“If we can detect any cancer at an earlier stage,” Silverman concludes, “then the survival rate is better, the quality of life is better and the prognosis is better.” 

Dental screening for oral cancer is critical. The earlier you catch it, the better off you are.

Vigilant dentists and hygienists can help save lives, oral cancer survivors attest

An Opening for Tumor Detection

Medical advances have allowed more people to survive longer after a cancer diagnosis than in years past. But in some cases, successful treatment results in heart and lung problems that do not show up for decades. 

Doctors have known for years that some chemotherapy drugs take a toll on the heart and lungs. However, these same agents are responsible for prolonging life. “Some of the drugs we give for certain diseases, like lymphomas or breast cancer, can weaken the heart muscle,” says Craig Earle, MD, medical director of the Lance Armstrong Foundation Adult Survivorship Clinic and a gastrointestinal oncologist at Dana-Farber Cancer Institute in Boston. “That may not be a problem initially. But over time as people age and other things affect the heart, they can end up with congestive heart failure.”

Medications in a class known as anthracyclines can harm the heart. Adriamycin (doxorubicin), commonly given to treat breast and childhood cancers, is an example.   

“It’s dose-dependent,” Earle says. “The more of the drug you have, the more likely this is to be a problem.”

For example, a cumulative dose throughout the course of treatment of Adriamycin equal to 300 mg/m2 or of its sister drug Ellence (epirubicin) at 600 mg/m2 is thought to create a higher risk.

Earle explains that anthracyclines cause the body to create free radicals that help the drug kill the cancer cells. While other cells in the body can neutralize the free radicals, the heart muscle lacks much neutralizing capacity. That leaves the free radicals available to hurt the heart muscle, leading to a weakened heart or accelerated plaque buildup in the arteries. 

Combining an anthracycline with radiation, Herceptin (trastuzumab) or some other drugs adds to the danger, research has indicated. Also, patients younger than 18 or older than 65 when treatment starts have an increased risk. An underlying heart condition also increases the chance of cardiac complications. 

Lee W. Jones, PhD, assistant research professor in the Department of Surgery at Duke University in Durham, N.C., suggests more attention should be paid to bringing high blood pressure or other cardiac-related conditions under control before starting cancer treatment.

Herceptin also has been associated with heart failure. The condition usually resolves after therapy ends but may persist long-term, Earle says. 

Jones cautions that other drugs used to treat breast cancer, such as Avastin (bevacizumab) or aromatase inhibitors, also may have some negative cardiovascular effects. 

“Those effects can be quite subtle. And we actually don’t see them right away,” Jones says. “We don’t know the long-term effects of these agents.” 

Treating testicular cancer or Hodgkin’s disease with Blenoxane (bleomycin) can result in pneumonitis, which is inflammation and subsequent scarring of the lung. Rather than a late effect, it usually occurs during treatment and higher doses appear to affect risk. Older patients, those with impaired kidney function, smokers and people with an underlying lung disease have a greater chance of developing lung problems. Doctors can choose other agents for these high-risk patients. 

Less data are available about long-term effects of platinum-based drugs such as cisplatin, used to treat testicular and other cancers. Cisplatin can cause damage to nerves (a condition called neuropathy) and to cells lining blood vessels. Studies also indicate the drug may increase risk of high blood pressure, lipid abnormalities, insulin resistance and obesity, which indirectly predispose people to heart attack and stroke. 

Radiation presents another risk. Beams aimed at the chest to fight lymphomas, breast or 

other cancers also can reach the heart and lungs. Radiation can weaken or scar the heart muscle or damage valves in the heart, research shows. Radiation also can accelerate coronary artery disease, creating rough spots in the arteries where fatty plaque can accumulate. Patients who have received such therapy may be more prone to suffering a heart attack at a younger age.  

Risk factors include associated use of anthracycline therapy and having a tumor close to the heart. Patients younger than 18 or with existing heart disease or cardiac risk factors have a greater chance of developing cardiac radiation effects. A total dose to the heart of 30 Gy or a daily dose fraction of more than 2 Gy bumps up the risk, research has found.

In addition, treatment for lymphoma or breast or lung cancer may result in radiation pneumonitis. That could develop into pulmonary fibrosis, a scarring of the tissue. Years later, heart or respiratory failure may occur as a result.

“I suspect the incidence may be less than for patients treated 20 or 25 years ago.”

Current data on such late toxicities come from patients treated 10 or 20 years ago. Oncologists, more aware of those dangers today, try to keep doses strong enough to work but low enough to avoid problems.

“Regimens are designed to limit late toxicities,” Vaughn says. 

Also, newer equipment allows radiation oncologists to target doses at the tumor with less fallout to other organs. Radiation specialists also try to keep daily doses equal to or below 2 Gy.

“There is still some incremental damage,” Jones says. “Radiotherapy is not benign.”

Earle is optimistic late effects will be less common in the future due to current practices. Vaughn agrees: “For the current generation of patients having treatment, I suspect the incidence may be less than for patients treated 20 or 25 years ago.” 

On the other hand, Jones is more pessimistic. He thinks some of the newer agents used to fight breast cancer also may result in late heart effects. He acknowledges a lack of data suggesting a long-term risk and bases his theory on how the current drugs work: The agents may weaken the heart. The tissue might not fully recover. Yet the patient may not have symptoms. Later, those patients might be at greater risk of heart disease.

“Treatments are longer and exposures to negative effects are greater than they used to be,” Jones says. 

Recently, the American Society of Clinical Oncology released a summary review of treatment late effects on patients’ hearts and lungs. An expert panel set out to develop guidelines for survivors’ care. But after reviewing the scientific data, Vaughn, a panel member, said the group discovered more research was needed. 

The lack of data leaves experts with little advice to offer cancer survivors beyond the basics. People should seek regular medical care. Simple blood pressure and lab tests can pick up changes early. If the screening shows a problem, the doctor can develop a treatment plan to manage blood pressure or cholesterol levels. 

Survivors should be sure to fully inform providers about their medical history. Secure a list of cancer treatments received, and share that list with any new doctor. Informed patients can remind a primary care provider about cancer treatment-associated risks and discuss whether any screenings would be beneficial. 

At the same time, lifestyle changes are key in lowering heart risks: Stop smoking. Eat a healthy diet. Drink alcohol only in moderation. Maintain a normal weight. Exercise. Control blood pressure. 

“All that will help,” Earle says. “There’s no downside to healthy living.”

Survivors should report to their doctors any shortness of breath, swelling or fatigue. A study by Steven Lipshultz, MD, of the University of Rochester Medical Center in New York, found many childhood cancer survivors were unaware of late-stage cardiac effects. Although the survivors felt tired during normal activities, they did not associate it with cancer treatment-related heart problems.

Vaughn, meanwhile, urges survivors not to panic. Late toxicities develop only in people who survive. Fear of late complications should not interfere with the chance of a cancer-free life. 

“Patients need to be cured,” Vaughn says. “Then we need to monitor carefully. You need to practice a healthy lifestyle and be aware of the problem. Together we will face this in the future.”

“People need to be mindful of the risk,” says David J. Vaughn, MD, associate professor of medicine at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia. However, he adds, “it should be remembered, these late toxicities are not that common.”

Certain drugs, as well as radiation to the chest, have been linked to late-effect heart and lung conditions. Both children and adults are susceptible to these complications, cancer specialists say.  

Cancer survivors sometimes face long-term cardiopulmonary fallout from treatment.

Debra Wood, RN

What to Watch For

Squashing a Queasy Stomach

An Opening for Tumor Detection

Heart & Lung Watch

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